The long-term goal of this laboratory is to understand the molecular mechanisms underlying synapse development and function. A number of model systems are used in our studies, including Xenopus nerve-muscle cultures, dissociated cultures of mammalian neurons, hippocampal slices and knockout mice. Our recent efforts focus on two closely related areas, using a combination of molecular biological and electrophysiological techniques: 1) to study the role of neurotrophic factors in synapse development and plasticity; 2) to isolate new genes and characterize new molecules that are involved in specific stages of synaptogenesis. We have discovered that the neurotrophin BDNF promotes the development of long-term potentiation, a cellular model for learning and memory. This effect is mediated by a potentiation of synaptic responses to high frequency stimulation. These results suggest that neurotrophins regulate synaptic maturation. We also demonstrated that endogenous synapsin I, a synaptic vesicle protein that is a target of neurotrophic regulation, is an important molecule mediating synapse maturation. Finally, we cloned the mammalian homolog of frequenin, a calcium binding protein involved in synaptic responses to high frequency stimulation.